WO2002074295A1 - Composition destinee a la prophylaxie ou au traitement de la demence senile - Google Patents

Composition destinee a la prophylaxie ou au traitement de la demence senile Download PDF

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Publication number
WO2002074295A1
WO2002074295A1 PCT/KR2002/000449 KR0200449W WO02074295A1 WO 2002074295 A1 WO2002074295 A1 WO 2002074295A1 KR 0200449 W KR0200449 W KR 0200449W WO 02074295 A1 WO02074295 A1 WO 02074295A1
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WO
WIPO (PCT)
Prior art keywords
curcumin
extract
senile dementia
preventing
curcuma aromatica
Prior art date
Application number
PCT/KR2002/000449
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English (en)
Inventor
Dong Keun Song
Tae Hee Lee
Original Assignee
Biosynergen, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Biosynergen, Inc. filed Critical Biosynergen, Inc.
Publication of WO2002074295A1 publication Critical patent/WO2002074295A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger

Definitions

  • the present invention relates to a composition for the prophylaxis and treatment of senile dementia, which comprises Curcumin or an extract of Curcuma aromatica SALISB. containing the Curcumin.
  • Alzheimer's disease one of the most common senile dementia, of which major causative factors are accumulation of beta-amyloid(A ⁇ ⁇ _ 2 ) in cerebrum and neurotoxicity derived therefrom (Selkoe, Annual Reviews in Neuroscience, 17, 489-517 (1994)).
  • beta-amyloid A ⁇ ⁇ _ 2
  • neurotoxicity derived therefrom
  • Curcuma aromatica SALISB is a pharmaceutical plant that has been long used for treatment of cholelithiasis, infectious hepatitis, hepatic pain and other disorder and as an analgesic and a diuretic.
  • Curcumin of the formula (I) below one of ingredients extracted from Curcuma aromatica SALISB., is known to have several advantageous effects including a liver function strengthening effect, an antibacterial effect of inhibiting pylori bacteria which are causative bacteria of gastric ulcer, a cholagogic effect to promote bile secretion, or diuretic function:
  • SALISB or Curcumin in preventing and treating senile dementia.
  • Another object of the present invention is to provide a functional food for preventing senile dementia.
  • an aspect of the present invention provides a pharmaceutical composition for preventing and treating senile dementia, comprising Curcumin or a pharmaceutically acceptable salt thereof as an effective ingredient.
  • a pharmaceutical composition for preventing and treating senile dementia which comprises an extract of Curcuma aromatica SALISB. containing Curcumin, and a pharmaceutically acceptable carrier.
  • a method of preventing and treating senile dementia by administering a therapeutically effective amount of Curcumin or a pharmaceutically acceptable salt thereof.
  • a method of preventing and treating senile dementia by administering a therapeutically effective amount of an extract of Curcuma aromatica SALISB. containing Curcumin.
  • a functional food for preventing senile dementia comprising Curcumin as an effective ingredient.
  • a functional food for preventing senile dementia comprising an extract of Curcuma aromatica SALISB. as an effective ingredient.
  • FIG. 1 is a graph showing the results of passive avoidance tests conducted on mice, which was administrated by an extract of Curcuma aromatica SALISB. in different amounts;
  • FIG. 1 is a graph showing the results of passive avoidance tests conducted on mice, which was administrated by Curcumin in different amounts.
  • Curcumin can be extracted from Curcuma aromatica SALISB. by the known method described in Rasmussen HB, et al., Planta Med., 66(4), 396-8 (2000), synthesized by the known methods described in various references including the Merck Index, or can be commercially available.
  • the Curcumin is generally prepared in various forms of pharmaceutically acceptable salts known in the art, including inorganic salts such as sodium salts, potassium salts, magnesium salts or calcium salts; organic salts of lysine, ethanol amine, N,N'-dibenzylethylene diamine and ⁇ -tocopherol; and esters of triterpene alcohols or plant sterols such as cycloartol ("oryzanol').
  • inorganic salts such as sodium salts, potassium salts, magnesium salts or calcium salts
  • organic salts of lysine, ethanol amine, N,N'-dibenzylethylene diamine and ⁇ -tocopherol such as esters of triterpene alcohols or plant sterols such as cycloartol ("oryzanol').
  • Curcumin is also contained in Curcuma aromatica SALISB.
  • the extract can be used in the form of an extract of Curcuma aromatica SALISB.
  • the extract can be prepared by a general method using a polar solvent, e.g., water; a low-grade alcohol such as methanol or ethanol; an organic solvent such as methylene chloride; or mixtures thereof.
  • a polar solvent e.g., water
  • a low-grade alcohol such as methanol or ethanol
  • an organic solvent such as methylene chloride
  • rhizomes of Curcuma aromatica SALISB. can be extracted with boiling water, or extracted with an organic solvent at 5 to 80°C (Celsius), preferably 30 to 55°C, for 30 minutes to 55 hours, preferably 30 minutes to 12 hours.
  • the resulted extract contains 0.01 to 3% by weight of Curcumin based on total weight of the extract.
  • To make the extract into powder it may be decompressed and dried.
  • Curcumin or an extract of Curcuma aromatica SALISB exhibits little toxicity in tests using mice, such as acute toxicity, nor side effects harmful to liver function.
  • a pharmaceutical composition for preventing and treating senile dementia can be prepared by mixing Curcumin or an extract of Curcuma aromatica SALISB. with a suitable carrier or an excipient which is pharmaceutically acceptable, or by diluting with a diluent.
  • Suitable examples of the carrier, the excipient and the diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, glucose, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, amorphous cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • the pharmaceutical composition may further include a filler, an anti-flocculating agent, a lubricant, a wetting agent, a flavor, an emulsifier, an antiseptic and the like.
  • the pharmaceutical composition of the present invention can be formulated by methods which are well known to those of skilled in the art so as to provide fast, continuous or delayed emission of the active ingredient upon administration into a mammal.
  • Formulations may be in the form of a pellet, a tablet, powder, a sachet, an elixir, a suspension, an emulsion, a solution, a syrup, an aerosol, a soft or hard gelatin capsule, a sterile injection or sterile powder.
  • the pharmaceutical composition can be administered by various routes such as orally, percutaneously, subcutaneously, and intravenously.
  • Curcumin may be administered at a dose of about 0.1 to 100 mg/kg of body weight per day
  • the extract of Curcuma aromatica SALISB. may be administered at a dose of about 1 to 1000 mg/kg of body weight per day.
  • the dose can be administrated totally once, or divisionally several times a day. It will be understood, however, the specific dose level of the active ingredient for any particular patient will be depend upon a variety of factors including route of administration, the age, sex, body weight, severity of the disease, etc., and thus the above-noted dose level does not limit the scope of the present invention in any way.
  • Curcumin or an extract of Curcuma aromatica SALISB can be added into a dietary supplementary or beverage for the purpose of preventing senile dementia.
  • the present invention also provides a functional food or drinkable composition for preventing senile dementia comprising an effective amount of Curcumin or an extract of Curcuma aromatica SALISB.
  • the foods to which the Curcumin or the extract of Curcuma aromatica SALISB. according to the present invention can be added for the purpose of preventing senile dementia include a variety of foods, drinkables, gums, teas, vitamin complexes and health-supplementary foods.
  • the functional food having a dementia preventing effect can be prepared by adding the Curcumin or extract of Curcuma aromatica SALISB.
  • the content of the Curcumin contained in the finally produced food or drinkables is preferably in the range of 0.001 to 0.1% by weight, and the content of the extract of Curcuma aromatica SALISB. contained in the finally produced food or drinkables is preferably in the range of 0.5 to 10% by weight.
  • Reference Example 1 Intracerebro ventricular (icy) injection ⁇ .%5 ⁇ gl5 ⁇ & beta-amyloid (1-42 amino acids) was injected intracerebroventricularly by using a 50/t Hamilton Syringe fitted with a 26-gauge needle until the tip of the needle was inserted 2.4 mm deep into the bregma of each mouse, according to the method described in Laursen & Belknap, J Pharmacol. Methods, 16, 355-357 (1986). For mice in a sham group, physiological saline in an equivalent amount was injected.
  • Reference Example 2 Passive avoidance test
  • a passive avoidance test was carried out by the following method described in Song et al., J. Neurochem, 71, 875-878 (1998).
  • a passive avoidance chamber consisting of an illuminated compartment and a dark compartment, in which means to deliver electrical shock are constructed on the bottom thereof.
  • an electrical shock (0.25 mA) was applied to the mouse for 1 second.
  • the mouse was again placed in the illuminated compartment and the latency to enter the dark compartment, that is, a passive avoidance response time, was measured.
  • the maximum limit of time was set to 300 seconds. If the mouse did not enter the dark compartment even after 300 seconds, the latency of 300 seconds was determined as the passive avoidance response time.
  • Preparation Example Preparation of extract of Curcuma aromatica SALISB. 300g of the root of Curcuma aromatica SALISB. (commercially available from Jeonghan Co., Ltd.), which was carefully selected and cut into small pieces, was added to 21 of water, followed by extracting at 100°C for 4 hours. The extracted product was collected, and moisture was removed therefrom using a decompressed reflux cooling tube, and then was completely dried using a freeze-dryer, yielding 25 g of extract powder of Curcuma aromatica SALISB.
  • Example 1 Prevention of senile dementia by the extract of Curcuma aromatica SALISB.
  • mice of 4-5 weeks old, weighing 20 to 25 g were divided into 4 groups composed of each 10 mice.
  • the extract of Curcuma aromatica SALISB. prepared in the Preparation Example, was dissolved in physiological saline and then orally administered five times in amounts of 0.25 g/kg and 0.5 g/kg (corresponding to 7.5 mg/kg and 15 mg/kg of Curcumin), respectively, at intervals of 10 hours.
  • an oral syringe for mouse was used for the oral administration of the extract.
  • after administering the extract of Curcuma aromatica SALISB was administered.
  • beta-amyloid (aa 1-42) (available from American Peptide Co.) was intracerebroventricularly injected into each mouse according to the method described in Reference Example 1.
  • physiological saline instead of the extract of Curcuma aromatica SALISB.
  • physiological saline instead of beta-amyloid
  • beta-amyloid was intracerebroventricularly injected.
  • mice in a control group physiological saline, instead of the extract of Curcuma aromatica SALISB., was orally administered in the same manner as described above, and beta-amyloid was then intracerebroventricularly injected in the same manner as described above.
  • Curcumin available from Sigma Co.
  • mice in two test groups Curcumin (available from Sigma Co.) was dissolved in corn oil and then orally administered five times in amounts of 10 mg/kg and 100 mg/kg, respectively, at intervals of 10 hours.
  • the oral administration of Curcumin was conducted by using an oral syringe for mouse.
  • 1.85 ⁇ g (5 l) of beta-amyloid (aa 1-42) was intracerebroventricularly injected into each mouse according to the method described in Reference Example 2.
  • mice in a sham group corn oil, instead of Curcumin, was orally administered, and physiological saline, instead of beta-amyloid, was intracerebroventricularly injected.
  • physiological saline, instead of Curcumin was orally administered in the same manner as described above, and beta-amyloid was then intracerebroventricularly injected in the same manner as described above.
  • FIG. 2 shows the results of the test, expressed with an average value of latencies for 10 mice.
  • the mice in the control group showed a significant reduction in passive avoidance response time (PO.001) compared with those in the sham group
  • the mice of the test groups administered with 10 g/kg and 100 g/kg of Curcumin, respectively showed significant increases in passive avoidance response time (P ⁇ 0.05 for mice administered with 10 mg/kg Curcumin and PO.01 for mice administered with 100 mg/kg Curcumin).
  • the passive avoidance response time increased in a Curcumin-concentration dependent way. It was confirmed from these results that Curcumin suppressed memory impairment due to accumulation of beta-amyloid.
  • Test Example 1 Oral toxicity test for the extract of Curcuma aromatica SALISB.
  • mice Each 20 of female and male ICR mice of 4 weeks old, were bred at an animal room with conditions of 22+ 3 ° C in temperature, 50+ 10% in relative humidity and 150-300 Lux in light intensity, for one week, and then divided into 4 groups each having 5 female mice and 5 male mice.
  • the extract of Curcuma aromatica SALISB. prepared according to Preparation Example was dissolved in physiological saline and then orally administered once in amounts of 300, 1,000 and 3,000 mg/kg, respectively.
  • a change in general symptoms and outbreak of dead animals were observed.
  • 7 days after administration the mice were killed and anatomized, following by examining their viscera with the naked eye.
  • On and after administration by measuring a change in body weight everyday, it was determined whether the animals showed a reduction in body weight due to the administered extract of Curcuma aromatica SALISB .
  • Hard gelatin capsule formulation cellulose 15 mg of isoflavone, 2.5 mg of Ginkgo biloba extract, 2 mg of extract of dried seed of Zizyphus spinosa, 0.25 mg of vitamin Bi, 0.3 mg of vitamin B 2 , 0.0025 mg of vitamin B 3 and 2.5 mg of magnesium stearate were completely mixed, followed by filling into a hard gelatin capsule, thereby forming a hard gelatin capsule formulation.
  • composition according to the present invention which comprises Curcumin or an extract of Curcuma aromatica SALISB. as an effective ingredient, can be advantageously used for preventing and treating senile dementia.

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Abstract

L'invention concerne une composition pharmaceutique destinée à la prévention et au traitement de la démence sénile, ainsi qu'un agent actif destiné à la prévention de la démence sénile, contenant de la curcumine ou un extrait de Curcumin aromatica SALISB. contenant la curcumine. La composition pharmaceutique et l'agent actif selon l'invention peuvent être employés de manière avantageuse dans la prévention et/ou le traitement de la démence sénile.
PCT/KR2002/000449 2001-03-16 2002-03-15 Composition destinee a la prophylaxie ou au traitement de la demence senile WO2002074295A1 (fr)

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KR1020010013726A KR20020073847A (ko) 2001-03-16 2001-03-16 쿠르쿠민 또는 울금 추출물을 포함하는 치매 예방 및치료용 조성물
KR2001/13726 2001-03-16

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003051380A2 (fr) * 2001-12-14 2003-06-26 Council Of Scientific And Industrial Research Composition destinee au traitement de troubles neurocerebrovasculaires
CN1312106C (zh) * 2003-03-28 2007-04-25 烟台同和医药科技有限公司 一种水溶性姜黄素复合盐的制备方法
WO2008048410A2 (fr) * 2006-09-19 2008-04-24 Human Biomolecular Research Institute Procédés diagnostiques et marqueurs génétiques pour la maladie d'alzheimer
WO2010106191A1 (fr) * 2009-03-20 2010-09-23 Bioxtract S.A. Composition pharmaceutique à propriétés anti-inflammatoires
US8895087B2 (en) * 2005-05-30 2014-11-25 Arjuna Natural Extracts, Ltd Composition to enhance the bioavailability of curcumin
US8993013B2 (en) * 2005-05-30 2015-03-31 Arjuna Natural Extracts, Ltd. Composition to enhance the bioavailability of curcumin
US9492402B2 (en) 2005-05-30 2016-11-15 Benny Antony Formulation of curcuminoids with enhanced bioavailability of curcumin, demethoxycurcumin, bisdemethoxycurcumin and method of preparation and uses thereof
US10159654B2 (en) 2005-05-30 2018-12-25 Arjuna Natural Extracts, Ltd Formulation of curcumin with enhanced bioavailability of curcumin and method of preparation and treatment thereof
US10286027B2 (en) 2005-05-30 2019-05-14 Arjuna Natural Extracts, Ltd. Sustained release formulations of curcuminoids and method of preparation thereof
US10543277B2 (en) 2005-05-30 2020-01-28 Arjuna Natural Private Limited Formulation of curcumin with enhanced bioavailability of curcumin and method of preparation and treatment thereof

Families Citing this family (5)

* Cited by examiner, † Cited by third party
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KR20020075122A (ko) * 2001-03-23 2002-10-04 권호정 울금으로부터 데메톡시커큐민을 추출하는 방법, 이러한방법으로 추출된 데메톡시커큐민, 이의 유도체 및 이들을포함하는 기능성 음료
KR100447668B1 (ko) * 2002-06-28 2004-09-08 현대약품공업주식회사 불용성 생리활성물질을 함유한 분산성 조각 젤리타입입자혼입 기능성음료 제조방법
KR100688907B1 (ko) * 2004-11-02 2007-03-02 한국화학연구원 울금 추출물 또는 커큐미노이드계 화합물을 유효성분으로 하는 벼 도열병 방제용 조성물
KR102008774B1 (ko) * 2016-07-07 2019-08-09 우석대학교 산학협력단 곰피, 강황, 건강 및 홍삼 추출물을 유효성분으로 함유하는 기억력 개선, 인지능력 개선, 치매 예방, 지연, 치료 또는 개선용 조성물
KR102046410B1 (ko) * 2017-06-26 2019-11-19 우석대학교 산학협력단 강황, 모과 및 건강 추출물을 유효성분으로 함유하는 기억력 개선, 인지능력 개선, 치매 예방, 지연, 치료 또는 개선용 조성물

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US5861415A (en) * 1996-07-12 1999-01-19 Sami Chemicals & Extracts, Ltd. Bioprotectant composition, method of use and extraction process of curcuminoids

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Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003051380A2 (fr) * 2001-12-14 2003-06-26 Council Of Scientific And Industrial Research Composition destinee au traitement de troubles neurocerebrovasculaires
WO2003051380A3 (fr) * 2001-12-14 2004-06-17 Council Scient Ind Res Composition destinee au traitement de troubles neurocerebrovasculaires
CN1312106C (zh) * 2003-03-28 2007-04-25 烟台同和医药科技有限公司 一种水溶性姜黄素复合盐的制备方法
US9878040B2 (en) 2005-05-30 2018-01-30 Arjuna Natural Extracts, Ltd. Composition to enhance the bioavailability of curcumin
US10159654B2 (en) 2005-05-30 2018-12-25 Arjuna Natural Extracts, Ltd Formulation of curcumin with enhanced bioavailability of curcumin and method of preparation and treatment thereof
US10543277B2 (en) 2005-05-30 2020-01-28 Arjuna Natural Private Limited Formulation of curcumin with enhanced bioavailability of curcumin and method of preparation and treatment thereof
US10512616B2 (en) 2005-05-30 2019-12-24 Arjuna Natural Private Limited Composition to enhance the bioavailability of curcumin
US10485843B2 (en) 2005-05-30 2019-11-26 Arjuna Natural Private Limited Composition to enhance the bioavailability of curcumin
US8895087B2 (en) * 2005-05-30 2014-11-25 Arjuna Natural Extracts, Ltd Composition to enhance the bioavailability of curcumin
US8993013B2 (en) * 2005-05-30 2015-03-31 Arjuna Natural Extracts, Ltd. Composition to enhance the bioavailability of curcumin
US9492402B2 (en) 2005-05-30 2016-11-15 Benny Antony Formulation of curcuminoids with enhanced bioavailability of curcumin, demethoxycurcumin, bisdemethoxycurcumin and method of preparation and uses thereof
US9861677B2 (en) 2005-05-30 2018-01-09 Arjuna Natural Extracts, Ltd. Composition to enhance the bioavailability of curcumin
US10286027B2 (en) 2005-05-30 2019-05-14 Arjuna Natural Extracts, Ltd. Sustained release formulations of curcuminoids and method of preparation thereof
WO2008048410A3 (fr) * 2006-09-19 2008-10-23 Human Biomolecular Res Inst Procédés diagnostiques et marqueurs génétiques pour la maladie d'alzheimer
WO2008048410A2 (fr) * 2006-09-19 2008-04-24 Human Biomolecular Research Institute Procédés diagnostiques et marqueurs génétiques pour la maladie d'alzheimer
JP2010504332A (ja) * 2006-09-19 2010-02-12 ヒューマン バイオモレキュラル リサーチ インスティテュート アルツハイマー病の診断方法及び遺伝子マーカー
RU2532384C2 (ru) * 2009-03-20 2014-11-10 Байокстракт С.А. Фармацевтическая композиция, проявляющая противовоспалительные свойства
WO2010106191A1 (fr) * 2009-03-20 2010-09-23 Bioxtract S.A. Composition pharmaceutique à propriétés anti-inflammatoires

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